Rutika Mehta, MD, MPH, medical oncologist, Moffitt Cancer Center, discusses which patients with esophageal squamous cell carcinoma (ESCC) may benefit most from the different frontline treatment options available and highlights key treatment developments with adjuvant immunotherapy plus chemotherapy.

Dr. Mehta on Frontline Treatments in ESCC

Chemotherapy alone has long been the standard first-line treatment for patients with metastatic ESCC, Mehta says. However, the phase 3 KEYNOTE-590 (NCT03189719) and CheckMate 648 (NCT03143153) trials have brought 2 new immunotherapy options to the frontline setting, Mehta explains. In KEYNOTE-590, patients with ESCC who received pembrolizumab (Keytruda) plus chemotherapy had a median overall survival (OS) of 12.6 months vs 9.8 months in those who received placebo plus chemotherapy. Additionally, the median progression-free survival (PFS) in this population was 6.3 months with the chemoimmunotherapy regimen vs 5.8 months with placebo.

CheckMate 648 investigated 2 frontline combinations: nivolumab (Opdivo) plus chemotherapy and nivolumab plus ipilimumab (Yervoy), a chemotherapy-free regimen. Across all enrolled patients with ESCC, this trial showed a median OS of 13.2 months with nivolumab plus chemotherapy vs 10.7 months with chemotherapy alone. CheckMate 648 also demonstrated a median OS benefit with nivolumab plus ipilimumab in this population, at 12.7 months vs 10.7 months with chemotherapy alone.

A small subset of patients with ESCC is eligible to receive the chemotherapy-free regimen of ipilimumab plus nivolumab, and the ideal patients for this regimen are those with minimal symptoms, Mehta notes. In patients with de novo metastatic disease who have their esophagus in place and present with dysphasia, a chemotherapy-free regimen may not be the most beneficial, Mehta elaborates. In addition, patients with heavy metastatic disease burden, such as multiple liver lesions or other visceral metastases, are not ideal candidates for this approach, Mehta says. However, patients on surveillance after esophagectomy who have isolated liver lesions, for example, may benefit from ipilimumab plus nivolumab.

Dr. Mehta on Future Developments in Adjuvant ESCC Treatment

An important development in the field of ESCC is the incorporation of adjuvant treatment after chemoradiation and surgery for patients with locally advanced disease, Mehta says. Adjuvant nivolumab is a new SOC in this setting, Mehta notes, and future data may demonstrate that the combination of chemoradiation and immunotherapy improves survival outcomes for patients with ESCC, Mehta explains.

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Rutika Mehta, MD, MPH, discusses which patients with esophageal squamous cell carcinoma may benefit most from the different frontline treatment options available and highlights key treatment developments with adjuvant immunotherapy plus chemotherapy.

Dr. Mehta on Frontline and Adjuvant Treatments in ESCC

Rutika Mehta, MD, MPH, a gastrointestinal medical oncologist at Moffitt Cancer Center, discusses a phase II trial that will combine ramucirumab (Cyramza) with TAS-102 in patients with advanced gastric and gastroesophageal junction cancer.

Patients who are eligible for this trial have progressed on a prior fluoropyrimidine and platinum-based doublet in the frontline setting, explains Mehta. These patients should have received at least 1 prior line of treatment, but not prior ramucirumab or TAS-102 therapy. Patients who are at high risk for bleed or have an arterial clot are not eligible, says Mehta.

The dosing for this trial is the standard dosing that was approved individually for ramucirumab and TAS-102. The most common adverse event with TAS-102 is neutropenia and toxicities related to ramucirumab include bleeding risk and additional bone marrow suppression with the combination, concludes Mehta.

Rutika Mehta, MD, MPH, discusses a phase II trial that will combine ramucirumab with TAS-102 in patients with advanced gastric and gastroesophageal junction cancer.

Dr. Mehta on TAS-102/Ramucirumab Combo Trial in Gastric/GEJ Cancer

Rutika Mehta, MD, MPH, gastrointestinal medical oncologist, Moffitt Cancer Center, discusses recent progress that has been made in advanced gastric cancer.

The field of gastric cancer is progressing at a rapid pace, and immuno-oncology is taking precedence in the field, says Mehta. Several novel combinations are under investigation. Patients have more first-, second-, and now, third-line options than ever before. The field is no longer dependent on the use of chemotherapy alone; rather, targeted treatments and immunotherapeutic agents have taken over the space.

Ramucirumab (Cyramza) is one such agent that, based on data from the phase III RAINBOW and REGARD trials, is FDA approved for use either alone or in combination with paclitaxel in the second-line setting. Notably, most patients with advanced disease will receive a fluoropyrimidine with a platinum-based agent in the frontline setting. This can cause neuropathy over time, which may be exacerbated by the combination of ramucirumab and paclitaxel in the second-line setting, cautions Mehta.

Dr. Mehta on Recent Progress Made in Advanced Gastric Cancer

Rutika Mehta, MD, MPH, gastrointestinal medical oncologist, Moffitt Cancer Center, discusses the rationale and design of a phase II study of TAS-102 (trifluridine/tipiracil; Lonsurf) in combination with ramucirumab (Cyramza) in patients with advanced, refractory gastric or gastroesophageal junction (GEJ) adenocarcinoma (NCT03686488).

Neurotoxicity and overlapping toxicities are fairly common between first- and second-line treatments, says Mehta. The goal is to develop novel combinations that do not result in such toxicities. Therefore, there are many clinical trials that have been emerging in this space in which investigators are exploring novel combinations with ramucirumab. One such combination is exploring ramucirumab plus the oral agent TAS-102.

The phase II trial is currently enrolling and has an anticipated accrual of 25 patients. To date, 7 patients have been accrued to the trial. Eligible patients have progressed on a prior fluoropyrimidine and platinum-based doublet in the first-line setting, says Mehta. Notably, patients could have received prior immunotherapy but could not have received prior ramucirumab or TAS-102 therapy. Additional exclusion criteria include a high bleeding risk and evidence of arterial clot, concludes Mehta.

Dr. Mehta on Rationale for a Phase II Trial of TAS-102/Ramucirumab in Gastric/GEJ Cancer

Rutika Mehta, MD, MPH, gastrointestinal medical oncologist at Moffitt Cancer Center, discusses the use of immunotherapy in patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma.

In the KEYNOTE-059 trial, patients who had progressed on 2 prior lines of therapy received pembrolizumab (Keytruda) monotherapy in the third-line setting. The agent resulted in an improvement in overall survival (OS), as well as an overall response rate of 13.3% in patients with PD-L1 positivity, says Mehta. These results served as the basis for the September 2017 FDA approval for use in this patient subset. Subsequently, results from the phase III KEYNOTE-061 study were announced. For this trial, investigators randomized patients to receive either pembrolizumab or paclitaxel. However, the trial failed to result in an improvement in OS or progression-free survival.

However, a subgroup analysis revealed that some subgroups showed benefit with the PD-1 inhibitor. This benefit was specific to patients with microsatellite instability-high tumors, as well as those with a CPS of ≥10 in the PD-L1—positive population, says Mehta. Although it is not recommended to use pembrolizumab in the second-line, a small subset of patients may derive benefit from the drug in that setting.

Rutika Mehta, MD, MPH

Articles

Dr. Mehta on Frontline and Adjuvant Treatments in ESCC

Dr. Mehta on TAS-102/Ramucirumab Combo Trial in Gastric/GEJ Cancer

Dr. Mehta on Recent Progress Made in Advanced Gastric Cancer

Dr. Mehta on Rationale for a Phase II Trial of TAS-102/Ramucirumab in Gastric/GEJ Cancer

Dr. Mehta on Immunotherapy in Gastric/GEJ Cancer